IDEAS home Printed from https://ideas.repec.org/a/nat/nature/v450y2007i7169d10.1038_nature06337.html
   My bibliography  Save this article

Human CtIP promotes DNA end resection

Author

Listed:
  • Alessandro A. Sartori

    (The Wellcome Trust and Cancer Research UK Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK)

  • Claudia Lukas

    (Institute of Cancer Biology and Centre for Genotoxic Stress Research, Danish Cancer Society, Strandboulevarden 49, DK-2100 Copenhagen, Denmark)

  • Julia Coates

    (The Wellcome Trust and Cancer Research UK Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK)

  • Martin Mistrik

    (Institute of Cancer Biology and Centre for Genotoxic Stress Research, Danish Cancer Society, Strandboulevarden 49, DK-2100 Copenhagen, Denmark)

  • Shuang Fu

    (Institute for Cancer Genetics, Columbia University, New York, New York 10032, USA)

  • Jiri Bartek

    (Institute of Cancer Biology and Centre for Genotoxic Stress Research, Danish Cancer Society, Strandboulevarden 49, DK-2100 Copenhagen, Denmark)

  • Richard Baer

    (Institute for Cancer Genetics, Columbia University, New York, New York 10032, USA)

  • Jiri Lukas

    (Institute of Cancer Biology and Centre for Genotoxic Stress Research, Danish Cancer Society, Strandboulevarden 49, DK-2100 Copenhagen, Denmark)

  • Stephen P. Jackson

    (The Wellcome Trust and Cancer Research UK Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK)

Abstract

In the S and G2 phases of the cell cycle, DNA double-strand breaks (DSBs) are processed into single-stranded DNA, triggering ATR-dependent checkpoint signalling and DSB repair by homologous recombination. Previous work has implicated the MRE11 complex in such DSB-processing events. Here, we show that the human CtIP (RBBP8) protein confers resistance to DSB-inducing agents and is recruited to DSBs exclusively in the S and G2 cell-cycle phases. Moreover, we reveal that CtIP is required for DSB resection, and thereby for recruitment of replication protein A (RPA) and the protein kinase ATR to DSBs, and for the ensuing ATR activation. Furthermore, we establish that CtIP physically and functionally interacts with the MRE11 complex, and that both CtIP and MRE11 are required for efficient homologous recombination. Finally, we reveal that CtIP has sequence homology with Sae2, which is involved in MRE11-dependent DSB processing in yeast. These findings establish evolutionarily conserved roles for CtIP-like proteins in controlling DSB resection, checkpoint signalling and homologous recombination.

Suggested Citation

  • Alessandro A. Sartori & Claudia Lukas & Julia Coates & Martin Mistrik & Shuang Fu & Jiri Bartek & Richard Baer & Jiri Lukas & Stephen P. Jackson, 2007. "Human CtIP promotes DNA end resection," Nature, Nature, vol. 450(7169), pages 509-514, November.
    • Handle: RePEc:nat:nature:v:450:y:2007:i:7169:d:10.1038_nature06337
    DOI: 10.1038/nature06337
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/nature06337
    File Function: Abstract
    Download Restriction: Access to the full text of the articles in this series is restricted.
    File URL: https://libkey.io/10.1038/nature06337?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    As the access to this document is restricted, you may want to search for a different version of it.

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Lorenzo Galanti & Martina Peritore & Robert Gnügge & Elda Cannavo & Johannes Heipke & Maria Dilia Palumbieri & Barbara Steigenberger & Lorraine S. Symington & Petr Cejka & Boris Pfander, 2024. "Dbf4-dependent kinase promotes cell cycle controlled resection of DNA double-strand breaks and repair by homologous recombination," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    2. Priya Kapoor-Vazirani & Sandip K. Rath & Xu Liu & Zhen Shu & Nicole E. Bowen & Yitong Chen & Ramona Haji-Seyed-Javadi & Waaqo Daddacha & Elizabeth V. Minten & Diana Danelia & Daniela Farchi & Duc M. D, 2022. "SAMHD1 deacetylation by SIRT1 promotes DNA end resection by facilitating DNA binding at double-strand breaks," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    3. Zita Gál & Stavroula Boukoura & Kezia Catharina Oxe & Sara Badawi & Blanca Nieto & Lea Milling Korsholm & Sille Blangstrup Geisler & Ekaterina Dulina & Anna Vestergaard Rasmussen & Christina Dahl & We, 2024. "Hyper-recombination in ribosomal DNA is driven by long-range resection-independent RAD51 accumulation," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    4. Rajashree A. Deshpande & Alberto Marin-Gonzalez & Hannah K. Barnes & Phillip R. Woolley & Taekjip Ha & Tanya T. Paull, 2023. "Genome-wide analysis of DNA-PK-bound MRN cleavage products supports a sequential model of DSB repair pathway choice," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    5. Bert Kooij & Fenna J. Wal & Magdalena B. Rother & Wouter W. Wiegant & Pau Creixell & Merula Stout & Brian A. Joughin & Julia Vornberger & Matthias Altmeyer & Marcel A. T. M. Vugt & Michael B. Yaffe & , 2024. "The Fanconi anemia core complex promotes CtIP-dependent end resection to drive homologous recombination at DNA double-strand breaks," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    6. Diego Dibitetto & Martin Liptay & Francesca Vivalda & Hülya Dogan & Ewa Gogola & Martín González Fernández & Alexandra Duarte & Jonas A. Schmid & Morgane Decollogny & Paola Francica & Sara Przetocka &, 2024. "H2AX promotes replication fork degradation and chemosensitivity in BRCA-deficient tumours," Nature Communications, Nature, vol. 15(1), pages 1-14, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:nature:v:450:y:2007:i:7169:d:10.1038_nature06337. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.